This proposal is a competitive renewal for the grant entitled, "Genetic Epidemiology of Prostate Cancer" The project involves a multidisciplinary group of researchers working on The Prostate Cancer Genetic Research Study (PROGRESS), an investigation of high-risk prostate cancer families aimed at mapping loci for the hereditary form of this disease. In addition, the study aims to further knowledge of the genetic epidemiology and molecular biology of prostate cancer. During the grant period covered by this continuation, we will utilize baseline and follow-up survey data, medical records, genotyping data, and DNA samples from members of PROGRESS families to address the following primary aims: 1) To complete linkage analyses of 421 genome-wide markers in 255 hereditary prostate cancer (HPC) families stratified by the presence of other primary cancers in the family; 2) To complete linkage and regression analyses of 421 genome-wide markers in 255 PROGRESS families, incorporating clinical data to search for loci associated with more aggressive phenotypes; 3) To genotype selected PROGRESS families for mutations in the BRCA2 gene to determine the role of such mutations in HPC; and, 4) To continue follow-up of members of 271 HPC families, with expansion of pedigrees and data collection as men newly diagnosed with prostate cancer are identified. In addition to the primary aims, we will address the following secondary aims: 5) To continue recruitment of African American families with prostate cancer; and, 6) To evaluate knowledge of and interest in genetic testing among affected and unaffected men. Genomic scan data, family cancer history data, and clinical data on prostate cases will be available. These data will be used to stratify families into more homogeneous subgroups for linkage analyses and to incorporate such data into regression models as quantitative traits. These approaches may lead to identification of new loci for HPC, including those linked to more aggressive disease. PROGRESS is a unique resource for addressing these aims and represents one of the largest collections of HPC families in the world. Finding such linkages and associated genes may provide novel and important insights into the underlying genetic epidemiology of prostate cancer, including the hereditary and sporadic forms of this common and complex disease.